The physicochemical characterization and drug delivery of lipid nanoparticles for topical and injectable dosage forms

• Main Authors: Yu Han Su, 蘇鈺涵
• Other Authors: J. Y. Fang
• Format: Others
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/91273782766158146158

碩士 === 長庚大學 === 天然藥物研究所 === 96 === Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are the new generation of nanoparticulate active substance vehicles and are attracting major attention as novel colloidal drug carriers. There are two purposes of this study. The first, we develop SLN and NLC, the nanoparticulate lipid based drug carriers, with increased skin permeation and controlled release properties for psoralens. The second, we investigate sustained release properties for tryptanthrin of nanoparticles and cytotoxicity of its tryptanthrin delivery system. For topical psoralen delivery (part I), SLN and NLC showed mean particle size of ~300 and ~200 nm respectively. Viscosity, polarity, and differential scanning calorimetry (DSC) studies were performed to characterize physicochemical properties of SLN and NLC. The viscosity of all nanoparticulate systems exhibited Newtonian behavior except NLC with Tween 80 and soybean phospholipids as the emulsfiers (NLC-Tw). According to the DSC thermograms, the melting peak of Precirol was shifted from 58 °C to 55 °C after incorporating squalene into the solid lipid cores (NLC) which suggests the defects in the crystalline lattice of the lipid cores and the smaller particle size. Three psoralen derivatives for psoriasis treatments were loaded in SLN and NLC for examining their skin permeation. The permeability of psoralens increased in the order of 8-methoxypsoralen (8-MOP) > 5-methoxypsoralen (5-MOP) > 4,5’,8-trimethylpsoralen (TMP). Both enhanced permeation and sustained release of psoralen delivery could be achieved by NLC. The in vitro permeation showed that NLC-Tw increased the 8-MOP flux 2.4 times over conventional emulsion. The hyperproliferative or psoriasis-like skin reproduced by repeated abrogation was also used as a permeation barrier. The animal model can predict the skin targeting ability of a drug applied on a disordered skin. For injection use tryptanthrin delivery (part II), NLC showed mean particle size lower and higher partition coefficient than SLN, thus increased the tryptanthrin release rate of NLC delivery system. NLC supplied sustained release of tryptanthrin delivery without burst release. Especially NLC-C which mixed squalene and Compritol as lipid materials showed highest released rate and best cytotoxicity effect. The images of confocal laser scanning microscopy confirmed that drug internalization into cell could be enhanced by the endocytosis of NLC. These results demonstrated that SLN and NLC can potentially be exploited as drug carrier systems for topical and intravenous use in the future.